Beyond symptomatic relief for chemotherapy-induced peripheral neuropathy: Targeting the source.
Beyond symptomatic relief for chemotherapy-induced peripheral neuropathy: Targeting the source.
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DOI：
10.1002/cncr.31248
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发表时间：
2018-06-01
期刊：
影响因子：
6.2
通讯作者：
Heijnen CJ
中科院分区：
文献类型：
--
作者：
Ma J;Kavelaars A;Dougherty PM;Heijnen CJ
化疗引起的周围神经病变（CIPN）是许多化疗药物的严重不良副作用，影响超过 60% 的癌症患者。此外，其中 20%-30% 的患者 CIPN 持续很长时间直至存活。美国食品和药物管理局 (FDA) 尚未批准任何药物可有效控制化疗引起的神经性疼痛。大多数用于治疗 CIPN 的测试药物旨在缓解症状，包括疼痛和感觉异常，但效果并不理想。我们建议，有必要对 CIPN 的病因有更透彻的了解，以便开发出有效的、基于机制的、缓解疾病的干预措施。重要的是，此类干预措施不应干扰化疗的抗肿瘤作用。线粒体是杆状细胞器，代表细胞的动力室，它们将氧气和营养物质转化为细胞能量“货币”三磷酸腺苷。此外，线粒体调节细胞死亡。神经元线粒体功能障碍和相关的硝基氧化应激代表了 CIPN 的重要最终共同途径。 在这里，我们讨论了通过使用新型潜在药物保护线粒体和/或抑制硝基氧化应激来预防或逆转 CIPN 的潜力，这些药物包括线粒体保护剂 Pifithrin-μ、组蛋白脱乙酰酶 6 抑制剂、二甲双胍、抗氧化剂、过氧亚硝酸盐分解催化剂和抗炎介质（包括白细胞介素 10）。这篇综述有望有助于缩小临床前研究与开发现实的新型治疗策略之间的差距，以预防或逆转化疗对（周围）神经系统的破坏性神经毒性作用。
Chemotherapy-induced peripheral neuropathy (CIPN) is a serious adverse side effect of many chemotherapeutic agents, affecting more than 60% of cancer patients. Moreover, CIPN persists long into survivorship in 20%‒30% of these patients. No drugs have been approved by the US Food and Drug Administration (FDA) to effectively manage chemotherapy-induced neuropathic pain. Most of the drugs tested for managing CIPN aim at symptom relief, including pain and paresthesia, yet are not very efficacious. We propose that there is a need to acquire a more thorough understanding of the etiology of CIPN so that effective, mechanism-based, disease-modifying interventions can be developed. Importantly, such interventions should not interfere with the antitumor effects of chemotherapy. Mitochondria are rod-shaped cellular organelles that represent the powerhouses of the cell, in that they convert oxygen and nutrients into the cellular energy “currency” adenosine triphosphate. In addition, mitochondria regulate cell death. Neuronal mitochondrial dysfunction and the associated nitro-oxidative stress represent crucial final common pathways of CIPN. Here we discuss the potential to prevent or reverse CIPN by protecting mitochondria and/or inhibiting nitro-oxidative stress with novel potential drugs, including the mitochondrial protectant pifithrin-μ, histone deacetylase 6 inhibitors, metformin, antioxidants, peroxynitrite decomposition catalysts, and anti-inflammatory mediators including interleukin-10. This review will hopefully contribute to bridging the gap between preclinical research and the development of realistic novel therapeutic strategies to prevent or reverse the devastating neurotoxic effects of chemotherapy on the (peripheral) nervous system.
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DOI：
10.1038/nrneurol.2014.77
发表时间：
2014-06
期刊：
Nature reviews. Neurology
影响因子：
--
作者：
Bennett GJ;Doyle T;Salvemini D
通讯作者：
Salvemini D
影响因子：
14.5
作者：
Fitzgerald, Julia C.;Zimprich, Alexander;Krueger, Rejko
通讯作者：
Krueger, Rejko
DOI：
10.1016/0031-6989(86)90147-5
发表时间：
1986-06-01
期刊：
PHARMACOLOGICAL RESEARCH COMMUNICATIONS
影响因子：
--
作者：
CHANTAL, T;NANCY, F;AIME, C
通讯作者：
AIME, C
影响因子：
82.9
作者：
d'Ydewalle, Constantin;Krishnan, Jyothsna;Van Den Bosch, Ludo
通讯作者：
Van Den Bosch, Ludo
影响因子：
7.4
作者：
Flatters, SJL;Bennett, GJ
通讯作者：
Bennett, GJ